THE SIR PROVIDED DR. MORODER WITH L-TELLUROMETHIONINE (.5G). AN IMPORTANT OBJECTIVE IN X-RAY ANALYSIS OF PROTEINS IS THE IMPROVEMENT OF PHASING BY ISOMORPHOUS REPLACEMENTS OF SELECTED AMINO ACID RESIDUES WITH ANALOGS OF DIVERSE ELECTRON DENSITY. OVERPRODUCTION OF PROTEINS IN E-COLI HAS BECOME AN ESTABLISHED TECHNIQUE AND USING METHIONINE AUXOTROPH E. COLI METHIONINE CAN POSSIBLE BE REPLACED BY VARIOUS ANALOGOUS RESIDUES. SUCCESSFUL BIOSYNTHETIC INCORPORATION OF SELENOMETHIONINE (HENDRICKSON, W.A. SCIENCE 254 (1991)51) AND RECENTLY OF TELLUROMETHIONINE (BOLES, J.D. ET AL. STRUCTURAL BIOLOGY 1 (1994) 283) HAS BEEN REPORTED INDICATING THIS APPROACH AS HIGHLY PROMISING. USING ANNEXIN AS MODEL PROTEIN WE WERE ALREADY SUCCESSFUL IN THE BIOSYNTHETIC REPLACEMENT OF METHIONINE WITH SELENOMETHIONINE AND NORLEUCINE (MANUSCRIPT IN PREPARATION). IT IS PLANNED TO USE THE SAME SYSTEM TO ATTEMPT INCORPORATION OF TELLUROMETHIONINE. THE TIME SCHEDULE OF THE PROJECT FORESEES PRELIMINARY EXPERIMENT TO ANALYZE THE FEASIBILITY OF INCORPORATION OF TELLUROMETHIONINE PARTICULARLY IN VIEW OF ITS FACILE OXIDATION. IF THESE EXPERIMENTS WILL LEAD TO POSITIVE RESULTS A SYNTHESIS OF TELLUROMETHIONINE WILL BE PERFORMED IN ORDER TO ALLOW FOR ROUTINE EXPERIMENTS